Submissions for variant NM_006371.5(CRTAP):c.444C>G (p.Tyr148Ter)

dbSNP: rs972668240

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000534680	SCV000641165	pathogenic	Osteogenesis imperfecta type 7	2023-09-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 465810). This variant has not been reported in the literature in individuals affected with CRTAP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr148*) in the CRTAP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CRTAP are known to be pathogenic (PMID: 17055431, 19862557, 24715559).
Neuberg Centre For Genomic Medicine, NCGM	RCV000534680	SCV004047549	likely pathogenic	Osteogenesis imperfecta type 7		criteria provided, single submitter	clinical testing	The stop gained variant c.444C>G (p.Tyr148Ter) in CRTAP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Tyr148Ter variant is novel (not in any individuals) in gnomAD exomes and is novel (not in any individuals) in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.444C>G in CRTAP is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.